spacer
spacer

PDBsum entry 1pd2

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Ligase PDB id
1pd2
Jmol
Contents
Protein chains
199 a.a. *
Ligands
GSH ×2
Waters ×297
* Residue conservation analysis
PDB id:
1pd2
Name: Ligase
Title: Crystal structure of hematopoietic prostaglandin d synthase with glutathione
Structure: Hematopoietic prostaglandin d synthase. Chain: 1, 2. Synonym: hpgds, spleen type pgds, glutathione dependent pgd engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Organ: spleen. Cellular_location: cytoplasm. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: de3.
Biol. unit: Dimer (from PQS)
Resolution:
2.30Å     R-factor:   0.204     R-free:   0.289
Authors: M.Miyano,H.Ago
Key ref:
Y.Kanaoka et al. (1997). Cloning and crystal structure of hematopoietic prostaglandin D synthase. Cell, 90, 1085-1095. PubMed id: 9323136 DOI: 10.1016/S0092-8674(00)80374-8
Date:
14-Dec-98     Release date:   13-Oct-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
O35543  (HPGDS_RAT) -  Hematopoietic prostaglandin D synthase
Seq:
Struc:
199 a.a.
199 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: E.C.2.5.1.18  - Glutathione transferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RX + glutathione = HX + R-S-glutathione
RX
+
glutathione
Bound ligand (Het Group name = GSH)
corresponds exactly
= HX
+ R-S-glutathione
   Enzyme class 3: E.C.5.3.99.2  - Prostaglandin-D synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (5Z,13E,15S)-9-alpha,11-alpha-epidioxy-15-hydroxyprosta-5,13-dienoate = (5Z,13E,15S)-9-alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate
(5Z,13E,15S)-9-alpha,11-alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
= (5Z,13E,15S)-9-alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate
      Cofactor: Glutathione
Glutathione
Bound ligand (Het Group name = GSH) corresponds exactly
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   2 terms 
  Biological process     lipid metabolic process   5 terms 
  Biochemical function     transferase activity     7 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0092-8674(00)80374-8 Cell 90:1085-1095 (1997)
PubMed id: 9323136  
 
 
Cloning and crystal structure of hematopoietic prostaglandin D synthase.
Y.Kanaoka, H.Ago, E.Inagaki, T.Nanayama, M.Miyano, R.Kikuno, Y.Fujii, N.Eguchi, H.Toh, Y.Urade, O.Hayaishi.
 
  ABSTRACT  
 
Hematopoietic prostaglandin (PG) D synthase is the key enzyme for production of the D and J series of prostanoids in the immune system and mast cells. We isolated a cDNA for the rat enzyme, crystallized the recombinant enzyme, and determined the three-dimensional structure of the enzyme complexed with glutathione at 2.3 A resolution. The enzyme is the first member of the sigma class glutathione S-transferase (GST) from vertebrates and possesses a prominent cleft as the active site, which is never seen among other members of the GST family. The unique 3-D architecture of the cleft leads to the putative substrate binding mode and its catalytic mechanism, responsible for the specific isomerization from PGH2 to PGD2.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Crystal Structure of Homodimer of Hematopoietic PGDS(A) Stereo Connolly surface of hematopoietic PGDS dimer complexed with GSH in CPK model. Oxygen, nitrogen, carbon, and sulfur atoms of GSH are colored red, blue, green, and yellow, respectively.(B) Ribbon diagram of hematopoietic PGDS dimer including bound GSH in CPK model. The dimer interface is composed of a hydrophobic side chain (F48) from one monomer and a hydrophobic cavity on the other (shown in ball and stick models with the dot surface). The hydrophobic cavity is formed by V91, T94, L127, D130, L131, Y134, and F141.(C) Closed-up view of the dimer interface in stereo. The electron density shows the difference Fourier map with omission of the side chains of F48, V91, T94, L127, D130, L131, Y134, and F141.(D) GSH difference Fourier map using the final hematopoietic PGDS model omitted GSH molecule.(E) GSH interaction diagram. The hydrogen bonds between the bound GSH and hematopoietic PGDS are shown by the break lines with their distances. The residues of D97′ belongs to the counterpart in the dimer.
Figure 5.
Figure 5. Reaction Mechanism of Isomerization from PGH[2] to PGD[2] by Hematopoietic PGDSA schematic drawing of the catalytic pocket of hematopoietic PGDS with PGH[2] shown in the same direction as in Figure 4B (panel 1). Pockets 1, 2, and 3 are colored yellow, blue, and green, respectively. The thiolate anion of bound GSH attacks the oxygen at C-11 of PGH[2] (panel 2). The putative reaction intermediate of PGH[2] with GSH is attacked by a certain base like bulk GSH in solvent (panel 3) to produce PGD[2] in a sterically restricted manner (panel 4).
 
  The above figures are reprinted by permission from Cell Press: Cell (1997, 90, 1085-1095) copyright 1997.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21428697 A.Oakley (2011).
Glutathione transferases: a structural perspective.
  Drug Metab Rev, 43, 138-151.  
  21425928 J.U.Flanagan, and M.L.Smythe (2011).
Sigma-class glutathione transferases.
  Drug Metab Rev, 43, 194-214.  
20022951 A.Shokeer, and B.Mannervik (2010).
Minor modifications of the C-terminal helix reschedule the favored chemical reactions catalyzed by theta class glutathione transferase T1-1.
  J Biol Chem, 285, 5639-5645.  
20122226 P.Paragi-Vedanthi, and M.Doble (2010).
Comparison of PGH2 binding site in prostaglandin synthases.
  BMC Bioinformatics, 11, S51.  
19131342 D.Irikura, K.Aritake, N.Nagata, T.Maruyama, S.Shimamoto, and Y.Urade (2009).
Biochemical, Functional, and Pharmacological Characterization of AT-56, an Orally Active and Selective Inhibitor of Lipocalin-type Prostaglandin D Synthase.
  J Biol Chem, 284, 7623-7630.  
19842715 H.J.Atkinson, and P.C.Babbitt (2009).
Glutathione transferases are structural and functional outliers in the thioredoxin fold.
  Biochemistry, 48, 11108-11116.  
  19359520 I.Mohri, K.Aritake, H.Taniguchi, Y.Sato, S.Kamauchi, N.Nagata, T.Maruyama, M.Taniike, and Y.Urade (2009).
Inhibition of prostaglandin D synthase suppresses muscular necrosis.
  Am J Pathol, 174, 1735-1744.  
19181746 M.Joo, M.Kwon, Y.J.Cho, N.Hu, T.V.Pedchenko, R.T.Sadikot, T.S.Blackwell, and J.W.Christman (2009).
Lipopolysaccharide-dependent interaction between PU.1 and c-Jun determines production of lipocalin-type prostaglandin D synthase and prostaglandin D2 in macrophages.
  Am J Physiol Lung Cell Mol Physiol, 296, L771-L779.  
19244215 M.W.Buczynski, D.S.Dumlao, and E.A.Dennis (2009).
Thematic Review Series: Proteomics. An integrated omics analysis of eicosanoid biology.
  J Lipid Res, 50, 1015-1038.  
19546224 T.Kumasaka, K.Aritake, H.Ago, D.Irikura, T.Tsurumura, M.Yamamoto, M.Miyano, Y.Urade, and O.Hayaishi (2009).
Structural basis of the catalytic mechanism operating in open-closed conformers of lipocalin type prostaglandin D synthase.
  J Biol Chem, 284, 22344-22352.
PDB codes: 2czt 2czu
19767395 Z.Mei, F.Wang, Y.Qi, Z.Zhou, Q.Hu, H.Li, J.Wu, and Y.Shi (2009).
Molecular determinants of MecA as a degradation tag for the ClpCP protease.
  J Biol Chem, 284, 34366-34375.  
18343821 K.J.Kim, M.C.Park, S.J.Choi, Y.S.Oh, E.C.Choi, H.J.Cho, M.H.Kim, S.H.Kim, D.W.Kim, S.Kim, and B.S.Kang (2008).
Determination of three-dimensional structure and residues of the novel tumor suppressor AIMP3/p18 required for the interaction with ATM.
  J Biol Chem, 283, 14032-14040.
PDB code: 2uz8
17682821 B.Blanchette, X.Feng, and B.R.Singh (2007).
Marine glutathione S-transferases.
  Mar Biotechnol (NY), 9, 513-542.  
17239574 M.Kapoor, F.Kojima, L.Yang, and L.J.Crofford (2007).
Sequential induction of pro- and anti-inflammatory prostaglandins and peroxisome proliferators-activated receptor-gamma during normal wound healing: a time course study.
  Prostaglandins Leukot Essent Fatty Acids, 76, 103-112.  
20477078 F.Kojima, M.Kapoor, S.Kawai, and L.J.Crofford (2006).
New insights into eicosanoid biosynthetic pathways: implications for arthritis.
  Expert Rev Clin Immunol, 2, 277-291.  
16310861 J.L.Herlong, and T.R.Scott (2006).
Positioning prostanoids of the D and J series in the immunopathogenic scheme.
  Immunol Lett, 102, 121-131.  
16547010 K.Aritake, Y.Kado, T.Inoue, M.Miyano, and Y.Urade (2006).
Structural and functional characterization of HQL-79, an orally selective inhibitor of human hematopoietic prostaglandin D synthase.
  J Biol Chem, 281, 15277-15286.
PDB code: 2cvd
16911359 M.Okano, T.Fujiwara, M.Yamamoto, Y.Sugata, R.Matsumoto, K.Fukushima, T.Yoshino, K.Shimizu, N.Eguchi, M.Kiniwa, Y.Urade, and K.Nishizaki (2006).
Role of prostaglandin D2 and E2 terminal synthases in chronic rhinosinusitis.
  Clin Exp Allergy, 36, 1028-1038.  
16639747 R.Singh, M.A.White, K.V.Ramana, J.M.Petrash, S.J.Watowich, A.Bhatnagar, and S.K.Srivastava (2006).
Structure of a glutathione conjugate bound to the active site of aldose reductase.
  Proteins, 64, 101-110.
PDB code: 2f2k
16552769 S.M.Valles, O.P.Perera, and C.A.Strong (2006).
Gene structure and expression of the glutathione S-transferase, SiGSTS1, from the red imported fire ant, Solenopsis invicta.
  Arch Insect Biochem Physiol, 61, 239-245.  
17093043 W.M.Qu, Z.L.Huang, X.H.Xu, K.Aritake, N.Eguchi, F.Nambu, S.Narumiya, Y.Urade, and O.Hayaishi (2006).
Lipocalin-type prostaglandin D synthase produces prostaglandin D2 involved in regulation of physiological sleep.
  Proc Natl Acad Sci U S A, 103, 17949-17954.  
15735307 A.M.Hansen, Y.Gu, M.Li, M.Andrykovitch, D.S.Waugh, D.J.Jin, and X.Ji (2005).
Structural basis for the function of stringent starvation protein a as a transcription factor.
  J Biol Chem, 280, 17380-17391.
PDB code: 1yy7
16189827 D.J.Schuller, Q.Liu, I.A.Kriksunov, A.M.Campbell, J.Barrett, P.M.Brophy, and Q.Hao (2005).
Crystal structure of a new class of glutathione transferase from the model human hookworm nematode Heligmosomoides polygyrus.
  Proteins, 61, 1024-1031.
PDB code: 1tw9
15822171 J.D.Hayes, J.U.Flanagan, and I.R.Jowsey (2005).
Glutathione transferases.
  Annu Rev Pharmacol Toxicol, 45, 51-88.  
15247628 N.Tetlow, A.Robinson, T.Mantle, and P.Board (2004).
Polymorphism of human mu class glutathione transferases.
  Pharmacogenetics, 14, 359-368.  
15454730 N.Tetlow, M.Coggan, M.G.Casarotto, and P.G.Board (2004).
Functional polymorphism of human glutathione transferase A3: effects on xenobiotic metabolism and steroid biosynthesis.
  Pharmacogenetics, 14, 657-663.  
15077012 N.Tetlow, and P.G.Board (2004).
Functional polymorphism of human glutathione transferase A2.
  Pharmacogenetics, 14, 111-116.  
12493770 L.Li, Y.Yang, and R.L.Stevens (2003).
RasGRP4 regulates the expression of prostaglandin D2 in human and rat mast cell lines.
  J Biol Chem, 278, 4725-4729.  
12627223 T.Inoue, D.Irikura, N.Okazaki, S.Kinugasa, H.Matsumura, N.Uodome, M.Yamamoto, T.Kumasaka, M.Miyano, Y.Kai, and Y.Urade (2003).
Mechanism of metal activation of human hematopoietic prostaglandin D synthase.
  Nat Struct Biol, 10, 291-296.
PDB codes: 1iyh 1iyi
11872752 A.S.Johansson, and B.Mannervik (2002).
Active-site residues governing high steroid isomerase activity in human glutathione transferase A3-3.
  J Biol Chem, 277, 16648-16654.  
11940059 A.Szczeklik, and M.Sanak (2002).
The role of COX-1 and COX-2 in asthma pathogenesis and its significance in the use of selective inhibitors.
  Clin Exp Allergy, 32, 339-342.  
12445497 H.N.Jabbour, R.W.Kelly, and S.C.Boddy (2002).
Autocrine/paracrine regulation of apoptosis in epithelial cells by prostaglandin E2.
  Prostaglandins Leukot Essent Fatty Acids, 67, 357-363.  
12371957 H.Vitzthum, I.Abt, S.Einhellig, and A.Kurtz (2002).
Gene expression of prostanoid forming enzymes along the rat nephron.
  Kidney Int, 62, 1570-1581.  
12244105 K.R.Kozak, B.C.Crews, J.D.Morrow, L.H.Wang, Y.H.Ma, R.Weinander, P.J.Jakobsson, and L.J.Marnett (2002).
Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, thromboxane, and prostacyclin glycerol esters and ethanolamides.
  J Biol Chem, 277, 44877-44885.  
11866090 S.Ejiri (2002).
Moonlighting functions of polypeptide elongation factor 1: from actin bundling to zinc finger protein R1-associated nuclear localization.
  Biosci Biotechnol Biochem, 66, 1.  
12148545 S.Saito, H.Tsuda, and T.Michimata (2002).
Prostaglandin D2 and reproduction.
  Am J Reprod Immunol, 47, 295-302.  
12482118 T.Kunz, N.Marklund, L.Hillered, and E.H.Oliw (2002).
Cyclooxygenase-2, prostaglandin synthases, and prostaglandin H2 metabolism in traumatic brain injury in the rat.
  J Neurotrauma, 19, 1051-1064.  
12388781 W.E.Mayer, T.Uinuk-Ool, H.Tichy, L.A.Gartland, J.Klein, and M.D.Cooper (2002).
Isolation and characterization of lymphocyte-like cells from a lamprey.
  Proc Natl Acad Sci U S A, 99, 14350-14355.  
11604524 A.J.Oakley, T.Harnnoi, R.Udomsinprasert, K.Jirajaroenrat, A.J.Ketterman, and M.C.Wilce (2001).
The crystal structures of glutathione S-transferases isozymes 1-3 and 1-4 from Anopheles dirus species B.
  Protein Sci, 10, 2176-2185.
PDB codes: 1jlv 1jlw
11705953 A.Sommer, M.Nimtz, H.S.Conradt, N.Brattig, K.Boettcher, P.Fischer, R.D.Walter, and E.Liebau (2001).
Structural analysis and antibody response to the extracellular glutathione S-transferases from Onchocerca volvulus.
  Infect Immun, 69, 7718-7728.  
11301410 D.S.Straus, and C.K.Glass (2001).
Cyclopentenone prostaglandins: new insights on biological activities and cellular targets.
  Med Res Rev, 21, 185-210.  
11067881 B.K.Kubata, M.Duszenko, Z.Kabututu, M.Rawer, A.Szallies, K.Fujimori, T.Inui, T.Nozaki, K.Yamashita, T.Horii, Y.Urade, and O.Hayaishi (2000).
Identification of a novel prostaglandin f(2alpha) synthase in Trypanosoma brucei.
  J Exp Med, 192, 1327-1338.  
10737945 J.U.Flanagan, W.King, M.W.Parker, P.G.Board, and G.Chelvanayagam (2000).
Ab initio calculations on hidden modulators of theta class glutathione transferase activity.
  Proteins, 39, 235-243.  
10824118 Y.Kanaoka, K.Fujimori, R.Kikuno, Y.Sakaguchi, Y.Urade, and O.Hayaishi (2000).
Structure and chromosomal localization of human and mouse genes for hematopoietic prostaglandin D synthase. Conservation of the ancestral genomic structure of sigma-class glutathione S-transferase.
  Eur J Biochem, 267, 3315-3322.  
11058767 Y.Urade, and O.Hayaishi (2000).
Biochemical, structural, genetic, physiological, and pathophysiological features of lipocalin-type prostaglandin D synthase.
  Biochim Biophys Acta, 1482, 259-271.  
  10548067 J.U.Flanagan, J.Rossjohn, M.W.Parker, P.G.Board, and G.Chelvanayagam (1999).
Mutagenic analysis of conserved arginine residues in and around the novel sulfate binding pocket of the human Theta class glutathione transferase T2-2.
  Protein Sci, 8, 2205-2212.  
9829702 J.U.Flanagan, J.Rossjohn, M.W.Parker, P.G.Board, and G.Chelvanayagam (1998).
A homology model for the human theta-class glutathione transferase T1-1.
  Proteins, 33, 444-454.  
9405674 Y.Eguchi, N.Eguchi, H.Oda, K.Seiki, Y.Kijima, Y.Matsu-ura, Y.Urade, and O.Hayaishi (1997).
Expression of lipocalin-type prostaglandin D synthase (beta-trace) in human heart and its accumulation in the coronary circulation of angina patients.
  Proc Natl Acad Sci U S A, 94, 14689-14694.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.